WO2005095453B1 - Specific binding members against synaptophysin - Google Patents

Specific binding members against synaptophysin

Info

Publication number
WO2005095453B1
WO2005095453B1 PCT/GB2005/001190 GB2005001190W WO2005095453B1 WO 2005095453 B1 WO2005095453 B1 WO 2005095453B1 GB 2005001190 W GB2005001190 W GB 2005001190W WO 2005095453 B1 WO2005095453 B1 WO 2005095453B1
Authority
WO
WIPO (PCT)
Prior art keywords
seq
domain
specific binding
binding member
variant
Prior art date
Application number
PCT/GB2005/001190
Other languages
French (fr)
Other versions
WO2005095453A2 (en
WO2005095453A3 (en
Inventor
Matthew Wright
Andy Porter
Original Assignee
Univ Aberdeen
Matthew Wright
Andy Porter
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from GB0407059A external-priority patent/GB0407059D0/en
Priority claimed from GB0416402A external-priority patent/GB0416402D0/en
Application filed by Univ Aberdeen, Matthew Wright, Andy Porter filed Critical Univ Aberdeen
Priority to EP05729772A priority Critical patent/EP1735347B1/en
Priority to US11/547,368 priority patent/US7871782B2/en
Priority to JP2007505627A priority patent/JP5020808B2/en
Priority to PL05729772T priority patent/PL1735347T3/en
Priority to CA2584608A priority patent/CA2584608C/en
Publication of WO2005095453A2 publication Critical patent/WO2005095453A2/en
Publication of WO2005095453A3 publication Critical patent/WO2005095453A3/en
Priority to KR1020067022596A priority patent/KR101205655B1/en
Publication of WO2005095453B1 publication Critical patent/WO2005095453B1/en
Priority to US12/974,899 priority patent/US20110165078A1/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/04—Drugs for skeletal disorders for non-specific disorders of the connective tissue
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/34—Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
    • C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
    • C07K2317/622—Single chain antibody (scFv)
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
    • G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/08—Hepato-biliairy disorders other than hepatitis
    • G01N2800/085—Liver diseases, e.g. portal hypertension, fibrosis, cirrhosis, bilirubin

Abstract

The present invention provides specific binding members that bind synaptophysin and which comprise: an antibody VH domain selected from the group consisting of the C1-3 VH domain (SEQ ID NO. 2) and a VH domain comprising a VH CDR3 with the amino acid sequence of SEQ ID NO. 12 and optionally one or more VH CDR's with an amino acid sequence selected from SEQ ID NO. 10 and SEQ ID NO. 11; and/or an antibody VL domain selected from the group consisting of the C1-3 VL domain (SEQ ID NO. 4) and a VL domain comprising one or more VL CDR's with an amino acid sequence selected from SEQ ID NO. 13, SEQ ID NO. 14 and SEQ ID NO. 15. The invention further provides related materials such as nucleic acids, kits and compositions, and also methods of use of the binding member, for instance in targeting entities to hepatic stellate cells which are implicated in liver fibrosis.

Claims

received by the International Bureau on 27 April 2006 (27.04.2006)
1. A specific binding member that binds synaptophysin and which comprises: an antibody VH domain selected from the group consisting of the Cl-3 VH domain (SEQ ID NO. 2) and a VH domain comprising a VH CDR3 with the amino acid sequence of SEQ ID NO. 12 and optionally one or more VH CDR' s with an amino acid sequence selected from SEQ ID NO. 10 and SEQ ID NO. 11; and/or an antibody VL domain selected from the group consisting of the Cl-3 VL domain (SEQ ID NO. 4) and a VL domain comprising one or more VL CDR' s with an amino acid sequence selected from SEQ ID NO. 13, SEQ ID NO. 14 and SEQ ID NO. 15.
2. A specific binding member according to claim 1 comprising an antibody VH domain comprising the VH CDR' s with the amino acid sequences of SEQ ID NO. 10, SEQ ID NO. 11 and SEQ ID NO. 12, which specific binding member competes for binding to synaptophysin with an synaptophysin binding domain of an antibody comprising the Cl-3 VH domain (SEQ ID NO. 2) and the Cl-3 VL domain (SEQ ID NO. 4).
3. A specific binding member according to claim 1 or claim 2 comprising the Cl-3 VH domain (SEQ ID NO. 2) .
4. A specific binding member according to claim 3 comprising the Cl-3 VL domain (SEQ ID NO. 4) .
5. A specific binding member according to any one of claims 1 to 3 that binds synaptophysin with affinity equal to or better than the affinity of an synaptophysin antigen-binding site formed by the Cl-3 VH domain (SEQ ID NO. 2) and the Cl-3
59 VL domain (SEQ ID NO. 4), the affinity of the specific binding member and the affinity of the antigen-binding site being as determined under the same conditions.
6. A specific binding member according to any one of claims 1 to 5 which binds an epitope within the amino acid sequence YPFRLHQVYFDAPSC (SEQ ID NO: 9) .
7. A specific binding member according to any one of claims 1 to 6 that comprises an scFv antibody molecule.
8. A specific binding member according to any one of claims 1 to 6 that comprises an antibody constant region.
9. A specific binding member according to claim 8 that comprises a whole antibody.
10. A specific binding member according to any one of claims 1 to 9 which comprises additional amino acids providing a further functional characteristic in addition to the ability to bind antigen.
11. A specific binding member according to any one of claims 1 to 10 which is conjugated to a detectable label, enzyme, or toxin, optionally via a peptidyl bond or linker.
12. A specific binding member according to claim 11 wherein the toxin is selected from the group comprising tributyl-tin and gliotoxin.
13. A specific binding member according to claim 11 wherein the detectable label is Fiτπ.
60
14. An isolated nucleic acid which comprises a nucleotide sequence encoding a specific binding member or antibody VH or VL domain of a specific binding member according to any one of claims 1 to 10.
15. A host cell transformed with nucleic acid according to claim 14.
16. A method of producing a specific binding member or antibody VH or VL domain, the method comprising culturing host cells according to claim 15 under conditions for production of said specific binding member or antibody VH or VL domain.
17. A method according to claim 16 further comprising isolating and/or purifying said specific binding member or antibody VH or VL variable domain.
18. A method according to claim 16 or claim 17 further comprising formulating the specific binding member or antibody VH or VL variable domain into a composition including at least one additional component.
19. A method of obtaining a specific binding member that binds synaptophysin, the method comprising providing by way of addition, deletion, substitution or insertion of one or more amino acids in the amino acid sequence of the Cl-3 VH domain (SEQ ID NO. 2) one or more VH domains each of which is an amino acid sequence variant of the Cl-3 VH domain, optionally combining one or more VH domain amino acid sequence variants thus provided with one or
61 more VL domains to provide one or more VH/VL combinations; and/or providing by way of addition, deletion, substitution or insertion of one or more amino acids in the amino acid sequence of the Cl-3 VL domain (SEQ ID NO. 4 ) a VL domain which is an amino acid sequence variant of the Cl-3 VL domain, and combining one or more VL domain amino acid sequence variants thus provided with one or more VH domains to provide one or more VH/VL domain combinations; and testing the VH domain amino acid sequence variants or VH/VL combination or combinations for to identify a specific binding member that binds synaptophysin.
20. A method of obtaining a specific binding member that binds synaptophysin, which method comprises: providing starting nucleic acids encoding one or more VH domains which either comprise a CDR3 to be replaced or lack a CDR3 encoding region, and combining said starting nucleic acid with a donor nucleic acid encoding the VH CDR3 amino acid sequence of SEQ ID NO. 12 such that said donor nucleic acid is inserted into the CDR3 region in the starting nucleic acid, so as to provide product nucleic acids encoding VH domains; or providing starting nucleic acids encoding one or more VL domains which either comprise a CDR3 to be replaced or lack a CDR3 encoding region, and combining said starting nucleic acid with a donor nucleic acid encoding the VL CDR3 amino acid sequence of SEQ ID NO. 15 such that said donor nucleic acid is inserted into the CDR3 region in the starting nucleic acid, so as to provide product nucleic acids encoding VL domains;
62 expressing the nucleic acids of said product nucleic acids encoding VH domains and optionally combining the VH domains thus produced with one or more VL domains to provide VH/VL combinations, and/or expressing the nucleic acids of said product nucleic acids encoding VL domains and combining the VL domains thus produced with one or more VH domains to provide VH/VL combinations; selecting a specific binding member comprising a VH domain or a VH/VL combination that binds synaptophysin; and recovering said specific binding member that binds synaptophysin and/or nucleic acid encoding the specific binding member that binds synaptophysin.
21. A method according to claim 19 or claim 20 wherein the specific binding member that binds synaptophysin is an antibody fragment comprising a VH domain and a VL domain.
22. A method according to claim 21 wherein the antibody fragment is an scFv antibody molecule.
23. A method according to claim 21 wherein the antibody fragment is an Fab antibody molecule.
24. A method according to claim 22 or claim 23 further comprising providing the VH domain and/or the VL domain of the antibody fragment in a whole antibody.
25. A method according to any one of claims 19 to 24 further comprising formulating the specific binding member that binds synaptophysin or an antibody VH or VL variable domain of the specific binding member that binds synaptophysin into a composition including at least one additional component.
63
26. A method according to any one of claims 16 to 25 further comprising binding a specific binding member that binds synaptophysin to synaptophysin or a fragment of synaptophysin .
27. A method comprising binding a specific binding member that binds synaptophysin according to any one of claims 1 to 13 to synaptophysin or a fragment of synaptophysin.
28. A method according to claim 26 or claim 27 wherein said binding takes place in vitro.
29. A method according to any one of claims 26 to 28 comprising determining the amount of binding of specific binding member to synaptophysin or a fragment of synaptophysin.
30. A method according to any one of claims 16 to 25 further comprising use of the specific binding member in the manufacture of a medicament for treatment of a disease or disorder characterised by liver fibrosis.
31. Use of a specific binding member in the manufacture of a medicament for treatment of a disease or disorder characterised by liver fibrosis, wherein the specific binding member is selected from:
(i) a specific binding member according to any one of claims 1 to 12,
(ii) a specific binding member that binds synaptophysin and which comprises: a variant antibody VH domain comprising a variant of the Cl-3 VH domain (SEQ ID NO. 2) or a variant of a VH CDR with an amino acid sequence selected from SEQ ID NO. 10; SEQ ID NO. 11 and SEQ ID NO. 12; and/or an variant antibody VL domain comprising a variant of the Cl-3 VL domain (SEQ ID NO. 4} or a variant of a VL CDR with an amino acid sequence selected from SEQ ID NO. 13, SEQ ID NO. 14 and SEQ ID NO. 15, wherein in each case the variant sequence comprises less than 20 alterations, less than about 15 alterations, less than about 10 alterations or less than about 5, 4, 3, 2 or 1 amino acid sequence alterations compared with the VH or VL domain or CDR, or
(iii) a specific binding member having an antigen-binding site which competes with the Cl-3 VH domain for binding to synaptophysin.
32. A method of treatment of a disease or disorder characterised by liver fibrosis, the method comprising administering a specific binding member to a patient with the disease or disorder or at risk of developing the disease or disorder, wherein the specific binding member is selected from: (i) a specific binding member according to any one of claims 1 to 12,
(ii) a specific binding member that binds synaptophysin and which comprises: a variant antibody VH domain comprising a variant of the Cl-3 VH domain (SEQ ID NO. 2) or a variant of a VH CDR with an amino acid sequence selected from SEQ ID NO. 10; SEQ ID NO. 11 and SEQ ID NO. 12; and/or
65 an variant antibody VL domain comprising a variant of the Cl-3 VL domain (SEQ ID NO. 4) or a variant of a VL CDR with an amino acid sequence selected from SEQ ID NO. 13, SEQ ID NO. 14 and SEQ ID NO. 15, wherein in each case the variant sequence comprises less than 20 alterations, less than about 15 alterations, less than about 10 alterations or less than about 5, 4, 3, 2 or 1 amino acid sequence alterations compared with the VH or VL domain or CDR, or
(iii) a specific binding member having an antigen-binding site which competes with the Cl-3 VH domain for binding to synaptophysin .
33. A method according to claim 32 wherein the specific binding member directs the delivery of a pharmaceutical composition to target hepatic stellate cells.
34. Use of a specific binding member and one or more reagents that allow determination of the binding of said member to hepatic stellate cells, in the manufacture of a diagnostic agent for the detection of a disease or disorder characterised by liver fibrosis, wherein the specific binding member is selected from: (i) a specific binding member according to any one of claims
1 to 13,
(ii) a specific binding member that binds synaptophysin and which comprises: a variant antibody VH domain comprising a variant of the
Cl-3 VH domain (SEQ ID NO. 2) or a variant of a VH CDR with an amino acid .sequence selected from SEQ ID NO. 10; SEQ ID
NO. 11 and SEQ ID NO. 12; and/or
66 an variant antibody VL domain comprising a variant of the Cl-3 VL domain (SEQ ID NO. 4) or a variant of a VL CDR with an amino acid sequence selected from SEQ ID NO. 13, SEQ ID NO. 14 and SEQ ID NO. 15, wherein in each case the variant sequence comprises less than 20 alterations, less than about 15 alterations, less than about 10 alterations or less than about 5, 4, 3, 2 or 1 amino acid sequence alterations compared with the VH or VL domain or CDR, or
(iii) a specific binding member having an antigen-binding site which competes with the Cl-3 VH domain for binding to synaptophysin .
35. A method of diagnosis of a disease or disorder characterised by liver fibrosis, the method comprising administering a specific binding member and one or more reagents that allow determination of the binding of said member to hepatic stellate cells, to a patient with the disease or disorder or at risk of developing the disease or disorder, wherein the specific binding member is selected from: (i) a specific binding member according to any one of claims 1 to 13,
(ii) a specific binding member that binds synaptophysin and which comprises: a variant antibody VH domain comprising a variant of the Cl-3 VH domain (SEQ ID NO. 2) or a variant of a VH CDR with an amino acid sequence selected from SEQ ID NO. 10; SEQ ID NO. 11 and SEQ ID NO. 12/ and/or an variant antibody VL domain comprising a variant of the Cl-3 VL domain (SEQ ID NO. 4 ) or a variant of a VL CDR with an amino acid sequence selected from SEQ ID NO. 13, SEQ ID NO. 14 and SEQ ID NO. 15,
67 wherein in each case the variant sequence comprises less than 20 alterations, less than about 15 alterations, less than about 10 alterations or less than about 5, 4, 3, 2 or 1 amino acid sequence alterations compared with the VH or VL domain or CDR, or
(iii) a specific binding member having an antigen-binding site which competes with the Cl-3 VH domain for binding to synaptophysin .
36. A diagnostic kit comprising a specific binding member and one or more reagents that allow determination of the binding of said member to hepatic stellate cells, wherein the specific binding member is selected from: (i) a specific binding member according to any one of claims 1 to 12,
(ii) a specific binding member that binds synaptophysin and which comprises: a variant antibody VH domain comprising a variant of the Cl-3 VH domain (SEQ ID NO. 2) or a variant of a VH CDR with an amino acid sequence selected from SEQ ID NO. 10; SEQ ID NO. 11 and SEQ ID NO. 12; and/or an variant antibody VL domain comprising a variant of the Cl-3 VL domain (SEQ ID NO. 4 ) or a variant of a VL CDR with an amino acid sequence selected from SEQ ID NO. 13, SEQ ID NO. 14 and SEQ ID NO. 15, wherein in each case the variant sequence comprises less than 20 alterations, less than about 15 alterations, less than about 10 alterations or less than about 5, 4, 3, 2 or 1 amino acid sequence alterations compared with the VH or VL domain or CDR,
(iii) a specific binding member having an antigen-binding site which competes with the Cl-3 VH domain for binding to synaptophysin .
68
37. A pharmaceutical composition comprising as active principle a specific binding member according to claims 1-12 in an effective amount, in conjunction with a pharmaceutically acceptable excipient.
69
PCT/GB2005/001190 2004-03-29 2005-03-29 Specific binding members against synaptophysin WO2005095453A2 (en)

Priority Applications (7)

Application Number Priority Date Filing Date Title
EP05729772A EP1735347B1 (en) 2004-03-29 2005-03-29 Specific binding molecules against synaptophysin
US11/547,368 US7871782B2 (en) 2004-03-29 2005-03-29 Specific binding members against synaptophysin
JP2007505627A JP5020808B2 (en) 2004-03-29 2005-03-29 Specific binding elements for synaptophysin
PL05729772T PL1735347T3 (en) 2004-03-29 2005-03-29 Specific binding molecules against synaptophysin
CA2584608A CA2584608C (en) 2004-03-29 2005-03-29 Specific binding members against synaptophysin
KR1020067022596A KR101205655B1 (en) 2004-03-29 2006-10-27 Specific binding members against synaptophysin
US12/974,899 US20110165078A1 (en) 2004-03-29 2010-12-21 Specific binding members against synaptophysin

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
GB0407059A GB0407059D0 (en) 2004-03-29 2004-03-29 Specific binding members against synaptophysin
GB0407059.5 2004-03-29
GB0416402.6 2004-07-22
GB0416402A GB0416402D0 (en) 2004-07-22 2004-07-22 Specific binding members against synaptophysin

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US12/974,899 Continuation US20110165078A1 (en) 2004-03-29 2010-12-21 Specific binding members against synaptophysin

Publications (3)

Publication Number Publication Date
WO2005095453A2 WO2005095453A2 (en) 2005-10-13
WO2005095453A3 WO2005095453A3 (en) 2006-04-06
WO2005095453B1 true WO2005095453B1 (en) 2006-12-21

Family

ID=35064446

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB2005/001190 WO2005095453A2 (en) 2004-03-29 2005-03-29 Specific binding members against synaptophysin

Country Status (8)

Country Link
US (2) US7871782B2 (en)
EP (1) EP1735347B1 (en)
JP (2) JP5020808B2 (en)
KR (1) KR101205655B1 (en)
CN (1) CN103130895A (en)
CA (1) CA2584608C (en)
PL (1) PL1735347T3 (en)
WO (1) WO2005095453A2 (en)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7871782B2 (en) * 2004-03-29 2011-01-18 The University Court Of The University Of Aberdeen Specific binding members against synaptophysin
ES2666550T3 (en) 2011-04-19 2018-05-07 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Human monoclonal antibodies specific for glypican 3 and their use
KR102006997B1 (en) * 2012-07-03 2019-08-02 한국생명공학연구원 A site-selective binding peptide for IgG Fc and a hybrid molecule comprising the same
MX370725B (en) * 2012-10-15 2019-12-20 Medimmune Ltd Antibodies to amyloid beta.
WO2023210585A1 (en) * 2022-04-25 2023-11-02 株式会社Jiksak Bioengineering Targeting agent
WO2024055010A1 (en) * 2022-09-08 2024-03-14 Board Of Regents, The University Of Texas System Compositions for treating cancer and methods of using the same

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3940209A1 (en) * 1989-12-05 1991-06-06 Boehringer Mannheim Gmbh METHOD FOR DETECTING A SMALL-CELL BRONCHIAL CARCINOMA
US5859205A (en) * 1989-12-21 1999-01-12 Celltech Limited Humanised antibodies
DE69222909T2 (en) * 1991-08-16 1998-03-12 Toshiba Kawasaki Kk Monoclonal antibody against a synaptophysin
GB9722131D0 (en) 1997-10-20 1997-12-17 Medical Res Council Method
DE10027695A1 (en) * 1999-05-27 2001-04-19 Max Delbrueck Centrum Vaccines against conformation-dependent or non-peptide antigens, based on DNA encoding peptide which mimics the antigen, useful e.g. as antitumor vaccines
WO2004019921A2 (en) * 2002-08-29 2004-03-11 University Of Southampton Use of apoptosis inducing agents in the preparation of a medicament for the treatment of liver diseases
US7871782B2 (en) * 2004-03-29 2011-01-18 The University Court Of The University Of Aberdeen Specific binding members against synaptophysin

Also Published As

Publication number Publication date
PL1735347T3 (en) 2013-04-30
KR101205655B1 (en) 2012-12-13
US20080274123A1 (en) 2008-11-06
JP2008506358A (en) 2008-03-06
CA2584608C (en) 2015-03-17
CN103130895A (en) 2013-06-05
WO2005095453A2 (en) 2005-10-13
KR20060135046A (en) 2006-12-28
JP2012162551A (en) 2012-08-30
US20110165078A1 (en) 2011-07-07
JP5020808B2 (en) 2012-09-05
EP1735347A2 (en) 2006-12-27
EP1735347B1 (en) 2012-11-07
WO2005095453A3 (en) 2006-04-06
CA2584608A1 (en) 2005-10-13
US7871782B2 (en) 2011-01-18

Similar Documents

Publication Publication Date Title
TWI796283B (en) Antibody constructs for msln and cd3
TWI793062B (en) Antibody constructs for dll3 and cd3
WO2021244089A1 (en) Sars-cov-2 spike protein binding molecule and application thereof
CN109963591B (en) B7H3 antibody-drug conjugate and medical application thereof
CN107216389B (en) anti-PD-L1 nano antibody and coding sequence and application thereof
KR102488220B1 (en) Matrix metalloproteinase substrates and other cleavable moieties and methods of use thereof
CN103747803B (en) Anti-AXL antibodies and application thereof
TWI526223B (en) Humanized axl antibodies
CN102257003B (en) For producing the genetic immunization of the immunoglobulin for cell-associated antigens such as P2X7, CXCR7 or CXCR4
KR20180101623A (en) PSMA and CD3 bispecific T cell engrafting antibody constructs
CN114106099A (en) Substrates and other cleavable moieties for proteolytic enzymes and U-type plasminogen activators and methods of use thereof
TW200804425A (en) Ligands that have binding specificity for EGFR and/or VEGF and methods of use therefor
US10738115B2 (en) Humanized antibodies transmigrating the blood-brain barrier and uses thereof
KR20160130435A (en) Insulin-like growth factor 1 receptor-specific antibodies and uses thereof
AU2017234275A1 (en) Protein a binding polypeptides, anti-EphA2 antibodies and methods of use thereof
WO2005095453B1 (en) Specific binding members against synaptophysin
US11608378B2 (en) Antibodies that bind integrin AVB8 and uses thereof
CA2401342A1 (en) Human antibodies against eotaxin and their use
JP2014515600A5 (en)
JP7186940B2 (en) Antibody variants that cross the blood-brain barrier and uses thereof
EP4257605A1 (en) Anti-tslp nanobody and use thereof
EP4299589A1 (en) Anti-human cd73 antibody and use thereof
JP2008506358A5 (en)
WO2021050871A1 (en) Antigen-binding protein constructs and uses thereof
US10435477B2 (en) Proprotein convertase subtilisin kexin type 9 binding proteins and uses thereof

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A2

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BW BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE EG ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NA NI NO NZ OM PG PH PL PT RO RU SC SD SE SG SK SL SM SY TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW

AL Designated countries for regional patents

Kind code of ref document: A2

Designated state(s): BW GH GM KE LS MW MZ NA SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IS IT LT LU MC NL PL PT RO SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
WWE Wipo information: entry into national phase

Ref document number: 2007505627

Country of ref document: JP

NENP Non-entry into the national phase

Ref country code: DE

WWW Wipo information: withdrawn in national office

Ref document number: DE

WWE Wipo information: entry into national phase

Ref document number: 11547368

Country of ref document: US

WWE Wipo information: entry into national phase

Ref document number: 1020067022596

Country of ref document: KR

WWE Wipo information: entry into national phase

Ref document number: 2005729772

Country of ref document: EP

Ref document number: 3134/KOLNP/2006

Country of ref document: IN

WWE Wipo information: entry into national phase

Ref document number: 200580017473.1

Country of ref document: CN

WWP Wipo information: published in national office

Ref document number: 2005729772

Country of ref document: EP

WWP Wipo information: published in national office

Ref document number: 1020067022596

Country of ref document: KR

WWE Wipo information: entry into national phase

Ref document number: 2584608

Country of ref document: CA